In this program project, we have outlined a series of studies which may have potential use in the design of more optimal therapeutic approaches in human solid tumors. In the cell kinetics projects, we have proposed to analyze the perturbation effects of various drugs on cell cycle in human lung, breast and head and neck cancers. We will correlate cytokinetic parameters with prognosis and response to therapy. We will compare simultaneously derived cell cycle parameters and estrogen and progesterone receptor proteins in breast cancer tissue. In animal kinetic studies, we will attempt to develop a comprehensive model to describe cytosine arabinoside and hydroxyurea by analyzing cell cycle perturbation effects with pulse and continuous infusion administration in tumor cells, bone marrow and ileum. These studies will be done in concert with biochemical pharmacologic analyses to determine the relationship of drug metabolites and perturbation. In a new tumor model, the MXT hormone dependent mouse mammary carcinoma, the relationship of cytokinetics and hormone receptors will be analyzed. The clinical program includes studies for lung cancer, prostate cancer and Phase II protocols for various solid tumors designed on the basis of cytokinetic concepts. These studies attempt to improve therapeutic results and serve as a basis to test pertubation effects of the modalities on cell populations.